History Of Solid Organ Transplantation Research Articles

Posttraumatic Growth in Youth, Young Adults, and Caregivers Who Experienced Solid Organ Transplant.

To explore posttraumatic growth (PTG) in pediatric patients who have undergone solid organ transplant (SOT) and their caregivers, and to examine potential correlates of PTG. Youth and young adults with a history of SOT (heart, kidney, liver) at least 1 month prior to participation and caregivers completed measures of PTG, demographic, and medical factors. In total, 59 youth (M = 12.68 years, SD = 1.91), 21 young adults (M = 19.37, SD = 0.82), and 95 caregivers (M = 37.95 years, SD = 9.37) participated. Overall, 67% of youth, 76% of young adults, and 89% of caregivers reported PTG within the medium to very high range. Appreciation of Life was the highest PTG subscale across all groups. Youth and caregiver PTG scores were significantly positively correlated. Religious affiliation and religious coping were positively associated with PTG for caregivers, and the relationship yielded large effect sizes for young adults. Caregivers of children with kidney transplants endorsed lower PTG than other organ types and caregivers of children who had an acute medical condition endorsed greater PTG than caregivers of children who had chronic illness. Findings suggest the pediatric SOT experience can yield positive changes such as a greater appreciation of life. Although small sample sizes may have led to reduced power for detecting significant findings for some analyses, results suggest religious, medical, and parent-child relationship factors are likely related to PTG in pediatric SOT and warrant future investigation.

Primary total hip arthroplasty complications and costs in liver transplant recipients: a matched analysis using a national database.

The number of liver transplant recipients (LTR) is worldwide increasing and, as the survival is improving as well, there is an increasing number of patients needing total hip arthroplasty (THA). There might be increased risks for this specific group of patients and due to their comorbidities costs might be higher too. Using a big national database outcome and cost of THA should be compared between liver transplant recipients and the general population. The study was performed using a collection of Medicare, Medicaid, and private insurance claims. Length of stay (LOS), 30-day readmissions, complications rates up to 5 years, and 90-day total cost of care between liver transplant recipients and matched non-transplant patients should be compared. All primary THAs from 2010 to 2019 were identified. 513 patients with a liver transplant before their THA were matched to 10,759 patients without a history of solid organ transplant at a 1:20 ratio based on age, sex, Charlson Comorbidity Index, obesity, and diabetes status. LTR had a longer average LOS (4.2 vs. 3.4 days, p < 0.001). There was no difference in the thirty-day readmissions (5.7% vs. 4.1%, p = 0.117) and 90-day dislocation rates (2.9% vs. 2.4%, p = 0.600). Total costs in the first ninety days after THA were not different between the LTR and controls (p = 0.756). These findings suggest that complications and costs are no major point of concern in patients with liver transplant that are operated with THA.

MP37-11 USE OF IMMUNE CHECKPOINT INHIBITORS IN SOLID ORGAN TRANSPLANT RECIPIENTS: A SCOPING REVIEW

You have accessJournal of UrologyRenal Transplantation & Vascular Surgery I (MP37)1 Sep 2021MP37-11 USE OF IMMUNE CHECKPOINT INHIBITORS IN SOLID ORGAN TRANSPLANT RECIPIENTS: A SCOPING REVIEW Alexander Anderson, Miranda Eubank, Diane Johnson, and Katie Murray Alexander AndersonAlexander Anderson More articles by this author , Miranda EubankMiranda Eubank More articles by this author , Diane JohnsonDiane Johnson More articles by this author , and Katie MurrayKatie Murray More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002046.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Immune checkpoint inhibitors (ICI) are an emerging treatment for numerous advanced diseases, but their safety and efficacy in immunosuppressed transplant patients is not known. This study undertakes a scoping review of research on ICI use in solid organ transplant (SOT) recipients to determine: 1) What is the effect of ICI on SOT recipients?; 2) What factors influence the effect of ICI on SOT recipients? METHODS: Data Sources: Searches of PubMed, Scopus and MEDLINE were performed with language restrictions on September 1, 2020. Study Selection: Any studies that reported the use of ICI in patients with a history of SOT were included irrespective of study design. Data Extraction: Three reviewers independently screened citations and performed data abstractions. A variety of variables were extracted from each publication. Data Synthesis: Of the total 549 screened articles, 50 articles met inclusion criteria with a sum of 101 cases of ICI use in patients with a history of SOT. RESULTS: Graft rejection occurred in 42% (n=42) of the cases. Kidneys were the most commonly rejected organ (n=28) with PD-1 inhibitors being the often-implicated etiology (n=32). Nearly 100% of the cases of graft rejection transpired within 2 months of ICI initiation. Patients on steroid monotherapy had higher rejection rates (72%, n=13) versus those on a steroid plus one or more immunosuppressive agents. In cases where graft preservation was pursued, salvage occurred 33% of the time (n=9). Regardless of graft outcomes, patient outcomes were overall poor due to advanced disease. In cases where patient outcome was reported, 71% (n=39) died directly from disease progression. CONCLUSIONS: ICI offer a promising therapeutic alternative to traditional chemoradiation for patients with advanced malignancies. However, their use in patients with a history of SOT poses a significant risk to the transplanted organ and cancer outcomes are worse in patients with SOT. Future studies are needed to delineate the risk and benefit more clearly. . . Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e650-e650 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Alexander Anderson More articles by this author Miranda Eubank More articles by this author Diane Johnson More articles by this author Katie Murray More articles by this author Expand All Advertisement Loading ...

Utility of Cytologic Assessment for Classification of Lymphoproliferative Disorders in Adult Patients with a History of Solid Organ Transplantation

Utility of Cytologic Assessment for Classification of Lymphoproliferative Disorders in Adult Patients with a History of Solid Organ Transplantation

Does immunosuppression increase perioperative wound morbidity in patients undergoing transversus abdominis release?

BackgroundTransversus abdominis release is an effective procedure for complex ventral hernias. As wound complications contribute to hernia recurrences, mitigating risk factors is vitally important for hernia surgeons. Although immunosuppression can impair wound healing, it has inconsistently predicted wound occurrences, and its effect on wound morbidity after a transversus abdominis release is unknown. MethodsPatients undergoing either an elective open or robotic bilateral transversus abdominis release with permanent synthetic mesh were retrospectively stratified by perioperative immunosuppression and secondarily by procedure type (open versus robotic) and immunosuppression. ResultsA total of 321 patients were included for analysis. Overall, 63 (19.6%) patients were on chronic immunosuppression, with history of solid-organ transplant being the most common indication (43 patients). Patients stratified by perioperative immunosuppression were well-matched with similar defect size (P = .97), body mass index ≥30 (P = .32), diabetes (P = .09), history of surgical site infection (P = .53), surgical approach (P = .53), and tobacco use history (P = .33). No differences between cohorts were elicited for any wound event when stratified by immunosuppression use. Similarly, no differences were elicited when cohorts were further stratified also by procedure type. ConclusionChronic immunosuppression is often viewed as a notable risk factor for wound occurrences after surgery. However, our data suggest immunosuppression may not significantly increase the risk of perioperative wound morbidity follow transversus abdominis release as previously predicted.

Abstract CT205: Design and rationale of a phase 1 study evaluating AMG 256, a novel, targeted, PD-1 antibody x IL-21 mutein bifunctional fusion protein, in patients with advanced solid tumors

Abstract Introduction Checkpoint inhibitors are a promising therapy for patients with solid tumors; however, many patients require additional therapies to maximize clinical benefit or overcome resistance. The type-1 cytokine interleukin-21 (IL-21) is a promising candidate for combination and has shown clinical activity in melanoma and renal cell cancer. IL-21 has also shown improved efficacy when combined with anti-programmed death (PD)-1 antibodies in preclinical models. AMG 256 is a bifunctional fusion protein comprising a PD-1-targeting antibody and IL-21 mutein designed to deliver IL-21 pathway stimulation to PD-1+ cells—a strategy that is designed to prime and extend the activity of cytotoxic and memory T cells and induce anti-tumor immunity. This first-in-human (FIH) study will assess safety, tolerability, and estimated dosing of AMG 256 monotherapy in patients with advanced solid tumors. Methods This is a FIH, multicenter, non-randomized, open-label, phase 1 study (NCT04362748) of AMG 256 in patients with advanced solid tumors. The planned sample size is approximately 100 patients in two parts: part 1 will evaluate safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and determine the maximum tolerated dose (MTD), part 2 will evaluate the MTD determined in part 1 to further characterize the safety profile and preliminary tumor response. AMG 256 will be delivered by intravenous (IV) infusion. Enrollment criteria include adults with life expectancy of &amp;gt; 3 months, ECOG performance status ≤ 2, histologically or cytologically confirmed metastatic or locally advanced solid tumors not amenable to curative treatment with surgery or radiation, and at least one measurable lesion ≥ 10 mm that has not undergone biopsy within 3 months of screening scan. Exclusion criteria include primary brain tumor, untreated or symptomatic brain metastases, currently receiving treatment in another investigational device or drug study, or less than 28 days since ending treatment on another investigational device or drug study, history of solid organ transplantation or major surgery within 28 days of study day 1, live vaccine therapy within 4 weeks prior to study day 1, and active infection requiring oral or IV therapy. The primary endpoints are incidence of dose-limiting toxicities and adverse events, MTD, and recommended phase 2 dose. Secondary objectives will evaluate PK parameters, preliminary antitumor activity (objective response, duration of response, progression-free survival, disease control rate, duration of stable disease, overall survival), and immunogenicity of AMG 256 via incidence of anti-AMG 256 antibodies. Citation Format: Greg Durm, Sophia Frentzas, Erik Rasmussen, Saltanat Najmi, Nooshin Hashemi Sadraei. Design and rationale of a phase 1 study evaluating AMG 256, a novel, targeted, PD-1 antibody x IL-21 mutein bifunctional fusion protein, in patients with advanced solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT205.

Trial eligibility in advanced hepatocellular carcinoma: Does it support clinical practice in underrepresented subgroups?

Although hepatocellular carcinoma is considered a highly lethal malignancy, recent therapeutic advances have been achieved during the last 10 years. This scenario resulted in an unprecedented improvement in survival for patients with advanced hepatocellular carcinoma, almost reaching 20-26 mo of overall survival after first-second line sequential treatment. The advent of the combination of atezolizumab with bevacizumab showed, for the first time, superiority over sorafenib with improvement in overall survival. However, first and second-line trials were correctly based on the premise that a strict selection of patients enhances the power to capture the positive effect of treatment by excluding competing risks for mortality such as liver failure, decompensated cirrhosis or other underlying medical conditions. As a result, the inclusion criteria used in clinical trials do not support the use of novel therapies in several real-world scenarios involving underrepresented subgroups, such as patients with unpreserved liver function, other comorbid conditions, a history of solid-organ transplantation, autoimmune disorders and those with a high risk of bleeding. The present text aims at discussing treatment strategies in these subgroups.

IMMU-07. “STROKE MIMICS” ARE NOT BENIGN IN IMMUNOCOMPROMISED CHILDREN

ObjectiveTo determine the clinical variances between strokes and stroke mimics in a pediatric immunocompromised population that consists of children with central nervous system (CNS) and non-CNS malignancies and a history of solid organ transplantation. MethodsWe performed a retrospective cohort analysis of stroke alert activations in patients with high-grade gliomas, low-grade gliomas, atypical teratoid rhabdoid tumors, rare CNS tumors, B-cell acute lymphoblastic leukemia, T-cell acute lymphoblastic leukemia, osteosarcoma, and solid organ transplants at St. Louis Children’s Hospital between February 2013 and September 2019. We categorized final diagnoses as strokes or stroke mimics. We classified diagnoses as a neurologic emergency if the diagnosis necessitated changes in management. ResultsOut of 217 stroke alerts, 31 alerts occurred for 28 patients meeting inclusion criteria. All final diagnoses constituted neurologic emergencies, including: stroke (39%), chemotherapy-related neurotoxicity (29%), tumor progression (19%), and seizures/posterior reversible encephalopathy syndrome (13%). Patients meeting inclusion criteria with strokes and stroke mimics presented similarly, with the exception of altered mental status, which was more prevalent in patients with strokes than stroke mimics (p = 0.03). One child received hyperacute thrombectomy for stroke. Only 58% of children with stroke mimics had complete resolution of their presenting neurologic symptoms. Children with strokes and stroke mimics had similar mortality incidences of 33% and 37%, respectively. ConclusionsAlthough all acute neurologic changes in immunocompromised children are not strokes, stroke mimics in this population are neither benign nor self-limited and carry long-term neurologic morbidity and mortality. This study highlights the utility of an acute stroke evaluation infrastructure and the need for acute and long-term neurology involvement in the care of these patients.

Checkpoint inhibition in immunosuppressed or immunocompromised patients with advanced cutaneous squamous cell carcinoma (CSCC): Data from prospective CemiplimAb-rwlc Survivorship and Epidemiology (C.A.S.E.) study.

9547 Background: Immunosuppressed and/or immunocompromised patients are at increased risk for solid tumors and cutaneous malignancies. Limited data exist on the safety and effectiveness of immune checkpoint inhibitors (ICIs) in these patients because they are frequently excluded from clinical trials. Here, we describe the safety and effectiveness results from the initial cohort of immunosuppressed and/or immunocompromised patients with advanced CSCC enrolled in the C.A.S.E. study (NCT03836105). Methods: C.A.S.E. is a prospective, real-world, multi-center, longitudinal study evaluating the effectiveness, safety, quality of life, and survivorship in patients with advanced CSCC treated with cemiplimab. Patients received cemiplimab 350 mg intravenously every 3 weeks per routine standard of care. Patient demographics, disease characteristics, immunosuppression, and relevant medical history were collected. Immunosuppressive regimens varied amongst patients. Investigator assessment of objective response rate (ORR), safety, and tolerability was conducted. Data from 26 immunosuppressed and/or immunocompromised patients with advanced CSCC treated with cemiplimab are presented. Recruitment is ongoing. Results: As of November 17, 2020, 121 patients were enrolled in the C.A.S.E. study, of which 26 patients (median age: 74 years [IQR: 71-84]; 85% male; 89% Caucasian) were designated as immunocompromised or immunosuppressed due to a history of solid organ transplant (n = 6), autoimmune disorder (n = 11), or hematologic malignancy (n = 9). Median duration of cemiplimab exposure was 14 months (IQR: 9.1–42, range: 0, 67). Among 19 immunocompromised or immunosuppressed patients who enrolled in C.A.S.E. prior to their third dose of cemiplimab, ORR per investigator assessment was 47% (95% CI: 24–71); 1 (5%) patient had complete response; 8 (42%) had partial response. One patient had a treatment-related serious adverse reaction of organ transplant rejection. One (3.8%) patient discontinued treatment due to increased alanine aminotransferase (not treatment-related). Immune-related AEs (irAEs) occurred in 23% of patients. No treatment-related AEs led to death. Conclusions: The safety, tolerability, and effectiveness of cemiplimab in this initial cohort of immunosuppressed and/or immunocompromised patients with advanced CSCC appear to be consistent with those observed in clinical trials that excluded these patients. Further follow-up and additional data would add to our general understanding of safety and effectiveness of anti-PD1 therapy in immunocompromised and/or immunosuppressed patient populations overall. Clinical trial information: NCT03836105.

Length of stay and surgical site complications are not increased after elective incisional hernia in patients with a history of solid organ transplantation.

The incidence of ventral hernia development after solid organ transplantation has been reported to be up to 30%. We aim to determine the impact of previous solid organ transplant on post-operative length of stay (LOS) and surgical site complications in elective ventral hernia repairs. A retrospective review of prospectively collected data from the Abdominal Core Health Quality Collaborative (ACHQC) was conducted to include all patients age 18years or older who underwent elective incisional hernia repair. Those with and without a history of solid organ transplantation were compared. The primary outcome was in-hospital LOS. Secondary outcomes included 30-day surgical site infection (SSI) rate, 30-day surgical site occurrence requiring procedural intervention (SSOPI) rate, 30-day overall post-operative complications and recurrence. The association between transplant and the LOS was tested with a negative binomial regression model adjusted for the demographic characteristics, comorbidities and hernia characteristics in the model. The population analyzed included 13,452 (98.79%) patients without a history of organ transplantation and 165 (1.21%) patients who had a history of organ transplantation. After adjusting for age, hernia width, BMI, gender, race, insurance type, ASA class, hypertension, dyspnea, OR time > 2h, abdominal wall SSI history, recurrent hernia, operative approach the median LOS was not significantly different between patients with a history of solid organ transplant [2.8 (2.6, 2.9) days] and those without [2.6days (2.2, 3.1)] (p = 0.5). The proportion of SSI (2.4% vs 4.04%; p = 0.42), SSOPI (4.2% vs 5.8%; p = 0.38) and recurrence (0.6% vs 0.4%, p = 0.51) was similar between both groups. Other remaining 30-day post-operative were negligible in our sample. There were no significant differences in LOS or infection rates between patients with and without a history of solid organ transplantation despite known risks of immunosuppression and chronic steroid use. Therefore, although these patients have many classic risk factors for poor outcomes, the data suggest that their history of solid organ transplantation should not preclude them from surgery.

Hepatitis E in solid organ transplant recipients: A systematic review and meta-analysis.

BACKGROUNDHepatitis E virus (HEV) infection is underdiagnosed due to the use of serological assays with low sensitivity. Although most patients with HEV recover completely, HEV infection among patients with pre-existing chronic liver disease and organ-transplant recipients on immunosuppressive therapy can result in decompensated liver disease and death.AIMTo demonstrate the prevalence of HEV infection in solid organ transplant (SOT) recipients. METHODSWe searched Ovid MEDLINE, EMBASE, and the Cochrane Library for eligible articles through October 2020. The inclusion criteria consisted of adult patients with history of SOT. HEV infection is confirmed by either HEV-immunoglobulin G, HEV-immunoglobulin M, or HEV RNA assay.RESULTSOf 563 citations, a total of 22 studies (n = 4557) were included in this meta-analysis. The pooled estimated prevalence of HEV infection in SOT patients was 20.2% [95% confidence interval (CI): 14.9-26.8]. The pooled estimated prevalence of HEV infection for each organ transplant was as follows: liver (27.2%; 95%CI: 20.0-35.8), kidney (12.8%; 95%CI: 9.3-17.3), heart (12.8%; 95%CI: 9.3-17.3), and lung (5.6%; 95%CI: 1.6-17.9). Comparison across organ transplants demonstrated statistical significance (Q = 16.721, P = 0.002). The subgroup analyses showed that the prevalence of HEV infection among SOT recipients was significantly higher in middle-income countries compared to high-income countries. The pooled estimated prevalence of de novo HEV infection was 5.1% (95%CI: 2.6-9.6) and the pooled estimated prevalence of acute HEV infection was 4.3% (95%CI: 1.9-9.4).CONCLUSIONHEV infection is common in SOT recipients, particularly in middle-income countries. The prevalence of HEV infection in lung transplant recipients is considerably less common than other organ transplants. More studies examining the clinical impacts of HEV infection in SOT recipients, such as graft failure, rejection, and mortality are warranted.

A Multicenter Evaluation of Ceftolozane/Tazobactam Treatment Outcomes in Immunocompromised Patients With Multidrug-Resistant Pseudomonas aeruginosa Infections.

BackgroundReal-world data assessing outcomes of immunocompromised patients treated with ceftolozane/tazobactam (C/T) are limited. This study evaluated treatment and clinical outcomes of immunocompromised patients receiving C/T for multidrug-resistant (MDR) Pseudomonas aeruginosa.MethodsThis was a 14-center retrospective cohort study of adult immunocompromised inpatients treated for ≥24 hours with C/T for MDR P. aeruginosa infections. Patients were defined as immunocompromised if they had a history of previous solid organ transplant (SOT), disease that increased susceptibility to infection, or received immunosuppressive therapies. The primary outcomes were all-cause 30-day mortality and clinical cure.ResultsSixty-nine patients were included; 84% received immunosuppressive agents, 68% had a history of SOT, and 29% had diseases increasing susceptibility to infection. The mean patient age was 57 ± 14 years, and the median (interquartile range) patient Acute Physiology and Chronic Health Evaluation II and Charlson Comorbidity Index scores were 18 (13) and 5 (4), respectively, with 46% receiving intensive care unit care at C/T initiation. The most frequent infection sources were respiratory (56%) and wound (11%). All-cause 30-day mortality was 19% (n = 13), with clinical cure achieved in 47 (68%) patients. Clinical cure was numerically higher (75% vs 30%) in pneumonia patients who received 3-g pneumonia regimens vs 1.5-g regimens.ConclusionsOf 69 immunocompromised patients treated with C/T for MDR P. aeruginosa, clinical cure was achieved in 68% and mortality was 19%, consistent with other reports on a cross-section of patient populations. C/T represents a promising agent for treatment of P. aeruginosa resistant to traditional antipseudomonal agents in this high-risk population.

Inpatient COVID-19 outcomes in solid organ transplant recipients compared to non-solid organ transplant patients: A retrospective cohort.

Immunosuppression and comorbidities might place solid organ transplant (SOT) recipients at higher risk from COVID-19, as suggested by recent case series. We compared 45 SOT vs. 2427 non-SOT patients who were admitted with COVID-19 to our health-care system (March 1, 2020 - August 21, 2020), evaluating hospital length-of-stay and inpatient mortality using competing-risks regression. We compared trajectories of WHO COVID-19 severity scale using mixed-effects ordinal logistic regression, adjusting for severity score at admission. SOT and non-SOT patients had comparable age, sex, and race, but SOT recipients were more likely to have diabetes (60% vs. 34%, p<.001), hypertension (69% vs. 44%, p=.001), HIV (7% vs. 1.4%, p=.024), and peripheral vascular disorders (19% vs. 8%, p=.018). There were no statistically significant differences between SOT and non-SOT in maximum illness severity score (p=.13), length-of-stay (sHR: 0.9 1.11.4 , p=.5), or mortality (sHR: 0.1 0.41.6 , p=.19), although the severity score on admission was slightly lower for SOT (median [IQR] 3 [3, 4]) than for non-SOT (median [IQR] 4 [3-4]) (p=.042) Despite a higher risk profile, SOT recipients had a faster decline in disease severity over time (OR = 0.76 0.810.86 , p<.001) compared with non-SOT patients. These findings have implications for transplant decision-making during the COVID-19 pandemic, and insights about the impact of SARS-CoV-2 on immunosuppressed patients.

Endogenous endophthalmitis in patients with intravenous opioid use: demographics and associated comorbidities.

To identify risk factors for endogenous endophthalmitis (EE) in hospitalized adults, under 65years of age, with a history of intravenous opioid use and non-ocular infection. The National Inpatient Sample Database was used to identify cases of EE with a recent history of intravenous opioid use disorder with associated non-ocular infection. Systemic and ocular comorbidities were identified using codes from the International Classification of Diseases, Ninth Revision (ICD-9). Descriptive and regression analyses were performed to evaluate the risk factors for EE using IBM SPSS 23. Of the 605,859 inpatients, 21-65years age, who had a history of recent opioid-IVDU and an associated IVDU-associated systemic infection, 363 (0.1%) had EE. Systemic comorbidities such as diabetes mellitus, mitral valve disease, aortic valve disease, history of cardiac valve transplantation, chronic kidney disease/renal failure, cirrhosis, active or previous radiation therapy, and history of solid organ transplantation were significantly more prevalent in patients with EE. A significantly increased risk of EE in intravenous opioid users was noted if they were of male gender (OR = 1.84), Asian/Pacific Islander ethnicity (OR = 4.41), had history of cirrhosis (OR = 2.33), active or history of radiation therapy (OR = 14.74), history of solid organ transplantation (OR = 5.91), candidemia (OR = 15.22), and infectious endocarditis (OR = 4.83). Conversely, concurrent alcohol use disorder (OR = 0.35) decreased the risk of EE. Various demographic variables and systemic comorbidities increased the risk of developing EE in inpatients with a history of intravenous opioid use with associated non-ocular infection.

Outcomes of COVID-19 in hospitalized solid organ transplant recipients compared to a matched cohort of non-transplant patients at a national healthcare system in the United States.

Data describing outcomes of solid organ transplant (SOT) recipients with coronavirus disease 2019 (COVID‐19) are variable, and the association between SOT status and mortality remains unclear. In this study, we compare clinical outcomes of SOT recipients hospitalized with COVID‐19 between March 10, and September 1, 2020, to a matched cohort of non‐SOT recipients at a national healthcare system in the United States (US). From a population of 43 461 hospitalized COVID‐19‐positive patients, we created a coarsened exact matched cohort of 4035 patients including 128 SOT recipients and 3907 weighted matched non‐SOT controls. Multiple logistic regression was used to evaluate association between SOT status and clinical outcomes. Among the 4035 patients, median age was 60 years, 61.7% were male, 21.9% were Black/African American, and 50.8% identified as Hispanic/Latino ethnicity. Patients with a history of SOT were more likely to die within the study period when compared to matched non‐SOT recipients (21.9% and 14.9%, respectively; odds ratio [OR] 1.93; 95% confidence interval [CI]: 1.18–3.15). Moreover, SOT status was associated with increased odds of receiving invasive mechanical ventilation (OR [95% CI]: 2.34 [1.51–3.65]), developing acute kidney injury (OR [95% CI]: 2.41 [1.59–3.65]), and receiving vasopressor support during hospitalization (OR [95% CI]: 2.14 [1.31–3.48]).

Invasive Fusariosis in Nonneutropenic Patients, Spain, 2000-2015.

Invasive fusariosis (IF) is associated with severe neutropenia in patients with concurrent hematologic conditions. We conducted a retrospective observational study to characterize the epidemiology of IF in 18 Spanish hospitals during 2000-2015. In that time, the frequency of IF in nonneutropenic patients increased from 0.08 cases per 100,000 admissions in 2000-2009 to 0.22 cases per 100,000 admissions in 2010-2015. Nonneutropenic IF patients often had nonhematologic conditions, such as chronic cardiac or lung disease, rheumatoid arthritis, history of solid organ transplantation, or localized fusariosis. The 90-day death rate among nonneutropenic patients (28.6%) and patients with resolved neutropenia (38.1%) was similar. However, the death rate among patients with persistent neutropenia (91.3%) was significantly higher. We used a multivariate Cox regression analysis to characterize risk factors for death: persistent neutropenia was the only risk factor for death, regardless of antifungal therapy.

198. Infective Endocarditis Among Solid Organ Transplant Recipients in the United States

BackgroundWith over 30,000 solid organ transplants (SOT) performed annually the United States alone, there is an urgent need to understand the risks and outcomes of infective endocarditis (IE) in SOT recipients.MethodsWe used data from the 2013–2017 Nationwide Readmissions Database (NRD). Hospitalizations associated with IE were identified using diagnosis and procedure codes. The cohort included all patients with IE, stratified by history of solid organ transplant (heart, liver, kidney, lung, intestines, pancreas). Outcomes included 60-day rates of mortality, (extracorporeal membrane oxygenation) ECMO deployment, thromboembolic events, length of stay, and inpatient costs. Regression models, weighted to account for the NRD sample design, were used to model associations between outcomes and transplant history, adjusting for patient age, sex, facility characteristics, comorbid conditions, and potential IE organism.ResultsA total of 175,682 hospitalizations associated with IE, corresponding to a national estimate of 345,236, were included. Of these, 1,299 (weighted estimate = 2,511) were associated with history of transplant. Transplant recipients were younger (54.2 vs. 59.4 years, p < 0.001), less likely to be female (33.2% vs. 40.1%), had higher rates of renal and liver disease (93.1% vs. 39.2% and 16.2% vs. 8.6%, respectively, p < 0.001 for both). The most common SOT organ (allowing for multiple organs) was kidney (75%) followed by liver (11.5%) and heart (10.5%). Compared to non-SOT patients with IE, SOT recipients with IE were associated with lower risk of mortality [adjusted relative risk (aRR): 0.74, 95% confidence interval (CI) (0.61, 0.89)], lower risk of prolonged mechanical ventilation [aRR 0.80 (0.68, 0.93)], 2.2 fewer inpatient days (-3.5 to -0.8) and $7,000 lower charges (-$9,700, -$4,300), after adjustment. ConclusionIE complicated by SOT history was associated with paradoxically better outcomes than IE in patients without SOT history. The selection process underlying receipt of transplant may partially explain these differences in outcomes.Disclosures Vance G. Fowler, Jr., MD, MHS, Achaogen (Consultant)Actavis (Grant/Research Support)Advanced Liquid Logics (Grant/Research Support)Affinergy (Consultant, Research Grant or Support)Affinium (Consultant)Allergan (Grant/Research Support)Ampliphi Biosciences (Consultant)Basilea (Consultant, Research Grant or Support)Bayer (Consultant)C3J (Consultant)Cerexa (Consultant, Research Grant or Support)Contrafect (Consultant, Research Grant or Support)Cubist (Grant/Research Support)Debiopharm (Consultant)Destiny (Consultant)Durata (Consultant)Forest (Grant/Research Support)Genentech (Consultant, Research Grant or Support)Integrated Biotherapeutics (Consultant)Janssen (Consultant, Research Grant or Support)Karius (Grant/Research Support)Locus (Grant/Research Support)Medical Biosurfaces (Grant/Research Support)Medicines Co. (Consultant)Medimmune (Consultant, Research Grant or Support)Merck (Consultant, Research Grant or Support)NIH (Grant/Research Support)Novadigm (Consultant)Novartis (Consultant, Research Grant or Support)Pfizer (Grant/Research Support)Regeneron (Consultant, Research Grant or Support)Tetraphase (Consultant)Theravance (Consultant, Research Grant or Support)Trius (Consultant)xBiotech (Consultant)

Retinal vein occlusion in solid organ transplant recipients. Study of 4 cases and literature review

Although retinal venous obstruction (RVO) has been primarily related to vascular risk factors and glaucoma, there are a few studies of RVO in patients with solid organ transplants. An analysis was performed on total of 331 patients who presented with RVO (branch RVO in 226 cases and central RVO in 105 cases) over a 10 year period, and the characteristics were compared with the 4 patients with a history of solid organ transplant (liver, renal, or bipulmonary) who presented with RVO. In this series, the onset of RVO in transplant patients occurred at earlier ages than in other patients with RVO (58 vs. 68 years, respectively), affected the central vein of the retina (100% vs. 32%), and was associated with diabetes mellitus (75% vs. 25%), as well as with steroidal (100% vs. 1%) and immunosuppressive (tacrolimus 75% vs. 0%) treatments.

EBV-Positive Primary CNS Lymphomas in Older Patients: Incidence, Characteristics, Tumor Pathology, and Outcomes across a Large Multicenter Cohort

EBV-Positive Primary CNS Lymphomas in Older Patients: Incidence, Characteristics, Tumor Pathology, and Outcomes across a Large Multicenter Cohort

Antifungal Prophylaxis and Risk for Invasive Mold Infections in Children with Hematologic Malignancies

Background: Invasive mold infections (IMI) are a leading cause of mortality in immunocompromised hosts. Children diagnosed with hematologic malignancies experience profound, prolonged neutropenia following intensive chemotherapy leading to augmented risk for infection-related outcomes, a risk that is mitigated with antimicrobial prophylaxis. Prior to the current study, we conducted a single-institution retrospective review of children diagnosed with acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), or lymphoma between 2006-2015 and determined the incidence of IMI at our institution to be 4.8% (47/976), with an exceptionally high incidence observed in patients with AML (8.1%, 9/111). This observation prompted a change in clinical practice to broaden mold coverage in high risk populations, including development of a risk-stratified algorithm for antifungal prophylaxis. For example, fluconazole was replaced with micafungin (inpatient) or voriconazole/posaconazole (outpatient) for newly diagnosed AML and relapsed/refractory ALL/AML, but still employed for populations at lower risk for IMI (infant ALL, Down syndrome ALL, ALL with steroid-induced diabetes). The objective of the present study was to evaluate the change in IMI incidence post-implementation of this algorithm, and to identify host factors contributing to risk for IMI in children with hematologic malignancies. Methods: We conducted a second retrospective review of children ≤ 21 years old and diagnosed with ALL, AML, or lymphoma during the follow-up period from 2016-2019, and diagnosed with IMI between 2016 and June 2020. To identify potential cases, we employed a strategy identical to the one used in the 2006-2015 review, specifically, a search of the electronic medical record utilizing ICD9 codes broadly inclusive of relevant cancer and fungal diagnoses. Each potentially eligible case was then reviewed for the following inclusion/exclusion criteria: diagnosis and treatment of ALL, AML, or lymphoma at Texas Children's Hospital, diagnosis of IMI that met criteria for 'proven' or 'probable' per the European Organization for Research and Treatment of Cancer/Mycoses Study Group and occurring prior to stem cell transplant, and no underlying immunodeficiency or history of solid organ transplant. Host and disease-related factors, as well as IMI incidence, were compared for 2006-2015 vs. 2016-2020 using a Chi-square, Fisher, or Student t-test as appropriate, and host factors predictive of IMI were assessed by multivariable linear regression. Results: The overall incidence of proven/probable IMI in children diagnosed with hematological malignancies between 2006-2019 was 4.2% (61/1456). The incidence of IMI decreased from 4.8% to 2.9% between 2006-2015 and 2016-2020. For specific diagnoses, the rate of IMI decreased from 5.0% to 3.6% (ALL, 35/705 vs. 10/276), from 1.9% to 1.4% (lymphoma, 47/976 vs. 14/480), and from 8.1% to 3.2% (AML, 9/111 vs. 2/62). No significant differences in host factor or disease-related characteristics were noted when comparing IMI cases in 2006-2015 vs. 2016-2020, nor were there differences in the proportion of patients in relapse at the time of IMI or taking antifungal prophylaxis. Substantial differences in representative mold species were noted between the two time periods, e.g. Aspergillus spp. accounted for 19/47 IMI from 2006-2015, but accounted for none of the IMIs diagnosed 2016-2020. In 2016-2020, 5/14 IMI were due to Trichosporon spp., with 4/14 Rhizopus spp., 2/14 Fusarium spp., 1/14 Curvularia spp., 1/14 Histoplasma spp., and 1 that met criteria for probable IMI. In multivariable analyses (Table 1), Hispanics were more likely to develop IMI than non-Hispanics (p=0.04, OR 1.94, CI 1.03-3.66), and those with lymphoma were less likely to develop an IMI than those with ALL (p=0.03, OR 0.33, CI 0.12-0.87). Patients diagnosed between 2016-2019 were substantially less likely to develop IMI than those diagnosed 2006-2015 (p=0.003, OR 0.33, CI 0.16-0.69). Conclusion: In this single-institution study, risk for IMI in children with hematologic malignancies declined significantly after implementation of an antifungal prophylaxis algorithm that broadened coverage for high risk populations. Hispanics were at higher risk for IMI than non-Hispanics, suggesting a need to investigate relevant factors contributing to this disparity. Table 1 Disclosures No relevant conflicts of interest to declare.